Villafañe is a surname. Notable people with the surname include:
Ángel de Villafañe (born 1504), the Spanish conquistador of Florida, Mexico, and Guatemala
Chunchuna Villafañe (born 1940), Argentine film and television actress, born in Buenos Aires, Argentina
Juan de Arphe y Villafañe (1535–1603), Spanish engraver, goldsmith, artist, anatomist and author
Luis Villafañe (born 1981), Puerto Rican professional basketball player
Santiago Villafañe (born 1988), Argentine footballer who plays for FC Midtjylland
